title: Impact of concomitant use of proton-pump inhibitors and thienopyridine derivatives on the antiplatelet effects.
abstract: BACKGROUND
  Although there has been an intense debate whether concomitant use of proton-pump inhibitors (PPIs) attenuates the antiplatelet effects of thienopyridine derivatives, the drug-drug interaction remains unclear in Japanese patients with coronary artery disease.
  
  
  RESULTS
  Platelet function test was performed in 461 patients who were scheduled for or had undergone stent implantation, treated with 100mg/day of aspirin and a thienopyridine (200mg/day of ticlopidine or 75 mg/day of clopidogrel) for at least 14 days. Adenosine diphosphate-induced platelet aggregation was evaluated with screen filtration pressure method, and the upper quartile of high platelet reactivity was defined as high on-treatment platelet reactivity (HPR). PPI use was at physician's discretion. Patients taking a thienopyridine plus a PPI (n=166) were older and had a higher incidence of acute coronary syndromes on admission compared with patients taking a thienopyridine without a PPI (n=295). The rate of HPR was higher in patients taking a thienopyridine plus a PPI than in patients taking a thienopyridine without a PPI (31% vs 21%, p=0.01). On multivariate logistic regression analysis, independent predictors of HPR were concomitant PPI use [odds ratio (OR): 1.66, 95% confidence interval (CI): 1.03-2.68], diabetes mellitus (OR: 1.76, CI: 1.11-2.81), and calcium channel blockers use (OR: 1.93, CI: 1.18-3.18). However, there was no significant difference in the rate of extremely high platelet reactivity [58 patients (12.5%) with PATI<4.0 μM] between patients treated with a thienopyridine plus a PPI and those without a PPI (14% vs 11%, NS).
  
  
  CONCLUSIONS
  HPR was frequently observed in Japanese patients treated with thienopyridines plus PPIs compared to those without PPIs. Further prospective studies are needed to estimate the risk of adverse cardiovascular events associated with concomitant use of PPIs and thienopyridines.
authors.affiliation: Division of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama 232-0024, Japan. c-kimura@urahp.yokohama-cu.ac.jp
authors.forename: Kengo
authors.initials: K
authors.lastname: Tsukahara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ebina
authors.forename: Masami
authors.initials: M
authors.lastname: Kosuge
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hibi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwahashi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Endo
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Maejima
authors.forename: Teruyasu
authors.initials: T
authors.lastname: Sugano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000368:Aged; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D015607:Stents; D058924:Thienopyridines / Q000008:administration & dosage* / Q000494:pharmacology*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D058924:Thienopyridines; D000077144:Clopidogrel; D013988:Ticlopidine